Controversial new research may overturn the standard treatment of men with advanced prostate cancer. Work presented at the European Association of Urology Annual Meeting 2014 indicates that men with advanced prostate cancer could have a better chance of surviving if they undergo treatment directed specifically at the prostate (so-called "radical" therapy) as well as hormonal treatment.

Prostate cancer is the second leading cause of cancer death in Western men. Advanced prostate cancer (where aggressive tumours have spread outside the prostate) usually results in death of the patient. The current standard method of treating advanced prostate cancer is with Androgen Deprivation Therapy (ADT). Androgen hormones, such as testosterone, are known to promote the growth of prostate cancer, and ADT reduces the level of these hormones in the body. Men with advanced prostate cancer who are treated with ADT on average survive around 5 years.

Men with advanced prostate cancer tend not to be offered Radical Prostatectomy (surgery to remove the whole prostate) or Radiotherapy, because their cancer will have already spread outside the primary tumour in the prostate, so ADT has been seen as a better "whole body" solution.

Now, new research from an international team led by Professor Peter Wiklund of the Karolinska Institute in Stockholm may lead to a significant revision of the standard treatment. The team analysed the records from the National Prostate Cancer Registry of Sweden, which contains virtually complete information on more than 98% of all prostate cancer cases in Sweden diagnosed from 1996 to 2010 - more than 109,000 men. From this database, they selected 2 groups of 699 men, which differed only in whether they had been offered ADT as a first treatment, or if they had first been treated by radical prostatectomy or radiotherapy followed by ADT.

They found almost two and a half times the number of deaths from prostate cancer in the group who had first been offered the standard hormonal treatment, in comparison to those who had undergone prostate-removing surgery prior to hormone treatment. After 14 years follow up, 231 of those treated with hormones alone had died of prostate cancer, whereas only 93 of those treated with the surgery or radiotherapy plus hormones had died of prostate cancer.

Total in study

Deaths from prostrate cancer after 14 years

Deaths from other causes after 14 years

Total deaths after 14 years

Treated with ADT (hormones) alone

699

231

90

321

Treated with RT (surgery) followed by ADT (hormones)

699

93

62

155

Table, from Sooriakumaran press release, EAU 2014

When they compared total deaths in the two groups, they found that twice as many men had died after hormone treatment (321), than with the combined treatment (155).

Presenting the work at the European Association of Urology in Stockholm, Dr Prasanna Sooriakumaran of the University of Oxford said: "We found that men with advanced prostate cancer have significantly improved survival after radical therapy plus hormonal treatment compared to hormonal treatment alone. We performed sensitivity tests to check that these results were unlikely to be due to abnormalities or deficiencies in the dataset, so we are confident in these results. This means we need to test these findings in a controlled study.

Currently, men with advanced prostate cancer are treated with hormonal therapy alone, and the median survival is around 5 years. A number of novel agents have been proposed in recent years, and these improve survival by months. Our research has the potential to improve survival outcomes by more than these novel treatments, and thus could represent a major advance in the field".

Professor Peter Wiklund further commented: "What we are presenting here is not only new but highly controversial, and will represent a paradigm shift in our understanding and management of advanced prostate cancer. Should the improved survival that combined treatment shown in this study be a real effect, then this could revolutionize the management of advanced prostate cancer. Our next step is to perform a multicenter randomized controlled trial to evaluate this question with the highest level evidence".

EAU Secretary General, Per-Anders Abrahamsson (Malmo) added: "This is potentially very important work, and needs to be followed up. If a larger trial confirms these results then it will be a major advance in the treatment of advanced prostate cancer".

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